Morphology of the prairie dog gallbladder: normal characteristics and changes during early lithogenesis.

Studies were undertaken to describe the normal structure of the prairie dog gallbladder and adjacent cystic duct, and then to determine sequential changes that occurred as abnormalities in bile composition developed during high cholesterol feeding. Control animals were fed a diet with trace cholesterol, while experimental animals were fed a diet enriched with 1.2% cholesterol for 1, 2, 3, or 4 weeks. Light microscopy and scanning and transmission electron microscopy were used to characterize morphologic changes at each time interval. Biliary lipid composition was altered in all experimental groups, evidenced by significant decreases in bile-acid-to-cholesterol ratios. Cholesterol crystals appeared in experimental bile at 1 and 2 weeks, while stones formed at 3 and 4 weeks. The cystic duct and neck of the gallbladder occasionally displayed goblet cells. Little mucus was demonstrable in principal cells of the gallbladder, but much more in those lining the cystic duct. After 2 weeks of lithogenic diet, there was an increase in mucus content and secretion from all areas, as well as an influx of polymorphonuclear and mononuclear leukocytes. Accumulation of plasma cells in the lamina propria was an especially prominent feature of experimental tissues. These results suggest that 1) there is regional heterogeneity in the mucus content of the gallbladder and cystic duct of the prairie dog, and 2) both regions respond to lithogenesis with mucus hypersecretion and acute and chronic inflammatory changes prior to the appearance of cholesterol gallstones.

The effects of lithogenic bile on gallbladder epithelium.

Prairie dogs were fed a 1.2% cholesterol diet for up to 24 weeks to evaluate the effects of lithogenic bile on the mucosa of the gallbladder. There was a progressive increase in the lithogenic index of the gallbladder bile (1.44 +/- 0.15 at 4 weeks, p less than 0.05). Fifty-five of 70 animals developed gallstones between the second and fourth week. Increasing stone burden was associated with a 27% (p less than 0.05) decrease in the electrical resistance of the epithelium and a 60% (p less than 0.05) decrease in net sodium transport when measured isotopically in an Ussing chamber (3 weeks). After 4 months, seven of ten animals developed inflammatory mucosal polyps characterized by a heavy infiltration of plasma cells into an expanded matrix. Cellular infiltration began as early as 2 weeks. These changes occurred without alterations in the ultrastructural appearance of the epithelium.

Common bile duct ligation in rabbit: a new model of acute cholecystitis description of histology and bile analysis.

The early stages of acute cholecystitis have been difficult to investigate due to the animal models developed and utilized over the past 60 years. A new model of animal acute cholecystitis induced by common bile duct ligation in the rabbit for 1 to 4 days produces histologic changes which are nearly identical to acute human cholecystitis. These changes include subserosal edema, hemorrhage, white cell infiltration, and dilatation of lymphatics. An inflammation scoring system is described with a range from 0 (not present) to 11 (the most severe). The inflammation score was 2 +/- 0.7 in control rising to 6.3 +/- 1.2 at 1 day of ligation and increasing further with time of duct ligation (P less than 0.01 all groups compared to control). Analysis of bile lithogenic index and concentrations of cholesterol, bile acids, and phospholipids showed no differences among control and experimental groups. Our findings show that the model of rabbit common bile duct ligation produces a histologic picture identical to human cholecystitis without chemical or physical manipulation of the gallbladder or significant changes in the bile lithogenic index.